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Viruses Jul 2023Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired... (Review)
Review
Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which comprise NP, to be essentially bacterial processes. As such, patients suspected of having either HAP or VAP are initially treated with broad-spectrum antibiotics, and few clinicians search for a possible culprit virus. Recent reports which build on earlier studies, however, indicate that viruses likely play an important role in NP. Studies employing viral diagnostics as part of the evaluation for NP indicate that common respiratory viruses can spread nosocomially and lead to HAP and VAP. Similarly, studies of the general epidemiology of respiratory viral infections, such as influenza, respiratory syncytial virus, adenovirus, and rhinovirus, confirm that these pathogens are important causes of NP, especially among immunosuppressed and pediatric patients. More importantly, these more contemporary analyses reveal that one cannot, based on clinical characteristics, distinguish a viral from a bacterial cause of NP. Additionally, viral HAP and VAP result in crude mortality rates that rival or exceed those reported in bacterial NP. Rigorous prospective, multicenter trials are needed to confirm the significance of respiratory viruses in NP, as are studies of novel therapeutics for these viral infections.
Topics: Humans; Child; Cross Infection; Prospective Studies; Healthcare-Associated Pneumonia; Adenoviridae; Respiratory Syncytial Virus, Human
PubMed: 37632017
DOI: 10.3390/v15081676 -
MMW Fortschritte Der Medizin May 2023
Review
Topics: Humans; Respiratory Syncytial Virus, Human; Lung; Respiratory Syncytial Virus Infections; Antibodies, Viral
PubMed: 37155064
DOI: 10.1007/s15006-023-2553-4 -
Science Translational Medicine Dec 2022In clinical trials, RSV prefusion F protein induced higher neutralizing antibodies and more activated memory B cells than postfusion F protein (Chang ). (Review)
Review
In clinical trials, RSV prefusion F protein induced higher neutralizing antibodies and more activated memory B cells than postfusion F protein (Chang ).
Topics: Humans; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus Infections; Antibodies, Viral; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus, Human
PubMed: 36542695
DOI: 10.1126/scitranslmed.ade9984 -
Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342 -
Frontiers in Immunology 2022Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal... (Review)
Review
Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.
Topics: COVID-19; Child; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Respiratory Syncytial Viruses; SARS-CoV-2
PubMed: 35359954
DOI: 10.3389/fimmu.2022.853009 -
Frontiers in Immunology 2022Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against...
Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against dengue, Ebola, influenza, pneumococcal, respiratory syncytial virus, rotavirus, shigella, tuberculosis and Zika virus.
Topics: Humans; Influenza Vaccines; Respiratory Syncytial Virus, Human; Influenza, Human; Zika Virus; Zika Virus Infection
PubMed: 36776392
DOI: 10.3389/fimmu.2022.1081107 -
BMC Infectious Diseases Jun 2020Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being...
BACKGROUND
Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age.
METHODS
The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies.
DISCUSSION
The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.
Topics: Antibodies, Monoclonal; Antiviral Agents; Child, Preschool; Drug Resistance, Bacterial; Female; Genome, Viral; Genotype; Humans; Immunization, Passive; Infant; Infant, Newborn; Male; Molecular Epidemiology; Polymorphism, Genetic; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 32591017
DOI: 10.1186/s12879-020-05175-4 -
The Lancet. Respiratory Medicine Oct 2021
Topics: Child, Preschool; Combined Modality Therapy; Humans; Infant; Internationality; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United Kingdom
PubMed: 34597586
DOI: 10.1016/S2213-2600(21)00411-2 -
Clinical Infectious Diseases : An... Jul 2021
Topics: Humans; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 32531025
DOI: 10.1093/cid/ciaa723 -
Viruses Dec 2020The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant... (Review)
Review
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
Topics: Animals; Biomarkers; Gene Expression Regulation, Viral; Host Specificity; Host-Pathogen Interactions; Humans; Immunity, Innate; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Viral Tropism; Virus Replication
PubMed: 33276587
DOI: 10.3390/v12121381